The proposed studies are designed to examine the mechanism underlying the selective muscle atrophy which occurs secondary to insulin deficiency or insulin resistance. The specific hypothesis is that insulin sensitivity and/or maximal responses are normally lower and are reduced ny insulin resistance to a greater extent in those muscle fibers which are most affected (primarily type II fast twitch, glycolytic) which compared to muscle fibers which are generally spared (type 1, slow twitch). If this is true, those fibers would be at greate risk of becoming "insulin deficient" whenever insulin or insulin receptors are decreased and would permit a greater expression of catabolic processes such as protein degadation. The major portion of this work will be done using steroid-induced myopathy in rats as a model of insulinresistance. Specific insulin binding will be measured in an array of tissues which are subject to or reisistant to the atrophy seen with insulin deficiency or resistance. Insulin sensitive pathways such as glucose and amino acid transport, protein and glycogen synthesis will be studied in vivo and in vitro in the same array of tissues. Dose response curves and maximal insulin effects will be constructed for these pathways and orrelated with the specific insulin binding data for individual tissues from control and steroid treated animals. After the patterns and degree of insulin resistance are characterized in a number of tissues, we plan to examine the time course of its development. Additionally, we plan to evaluate the effectiveness of diet manipulation, exercise and insulin therapy in ameliorating the myopathy which accompanies steroid therapy. The clinical relevance of this study lies in the fact that steroids are commonly used, and it has been assumed that the muscle wasting and weakness are due to a direct action of the steroids on muscle. If our hypothesis that the muscle wasting is secondary to the induced insulin resistance rather than the steroid is found to be true, then this wasting may be reduced by concomitant insulin therapy without reducing the steroid dose.